Abstract

Purpose of Review

In this review, we describe a shared requirement for resident microbiota to stimulate intestinal epithelial cell proliferation revealed in germ-free mice, zebrafish, and fruit flies. We seek to understand the extent to which these hosts respond to their microbiota through shared mechanisms, reflecting ancient animal epithelial tissue adaptations to microbial coexistence, versus through host-specific specializations.

Recent Findings

We find examples of host-specific microbial pro-proliferative stimuli, but across hosts, these stimuli are often sensed via innate immune pathways involving Myd88 and NFkappaB. These sensing pathways appear to stimulate a diversity of conserved effectors of epithelial proliferation and repair including reactive oxygen species, Beta-catenin, Jak/Stat, and mTOR signaling.

Summary

We conclude that diverse microbial signals are sensed through host innate immune pathways to induce conserved programs of epithelial proliferation and repair. Harnessing these responses will provide new avenues for treating underdeveloped or injured epithelia.

• Jones TA, Hernandez DZ, Wong ZC, et al (2017) The bacterial virulence factor CagA induces microbial dysbiosis that contributes to excessive epithelial cell proliferation in the Drosophila gut. PLoS Pathog, In Press. This study shows that a dysbiotic microbiota stimulates excessive cell proliferation in the Drosophila intestine through a mechanism that requires the presence of two members, aLactobacillusand anAcetobacter, whereas each strain on its own is not pro-proliferative.Google Scholar